U.S. patent number 7,059,348 [Application Number 10/438,282] was granted by the patent office on 2006-06-13 for drug delivery system.
This patent grant is currently assigned to Fluidigm Corporation. Invention is credited to Avtar S. Nat.
United States Patent |
7,059,348 |
Nat |
June 13, 2006 |
Drug delivery system
Abstract
An implantable drug delivery system has a housing, a collapsible
reservoir, a microfabricated flow channel, and at least one magnet.
The collapsible reservoir is disposed in the housing. The
microfabricated flow channel is connected at one end to the
collapsible reservoir and opens at an external surface of the
housing. The magnet is disposed within the housing adjacent a
membrane defining the flow channel and is movable in response to a
magnetic force to deflect the membrane into the flow channel for
inhibiting drug flow from the collapsible reservoir to the external
surface of the housing, and for pumping drug flow from the
collapsible reservoir to the external surface of the housing.
Inventors: |
Nat; Avtar S. (Saratoga,
CA) |
Assignee: |
Fluidigm Corporation (South San
Francisco, CA)
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Family
ID: |
34915372 |
Appl.
No.: |
10/438,282 |
Filed: |
May 13, 2003 |
Prior Publication Data
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Document
Identifier |
Publication Date |
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US 20050197652 A1 |
Sep 8, 2005 |
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Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
Issue Date |
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60380784 |
May 13, 2002 |
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Current U.S.
Class: |
137/597;
251/61.1; 604/891.1 |
Current CPC
Class: |
A61K
9/0009 (20130101); A61K 9/0024 (20130101); A61K
9/703 (20130101); Y10T 137/88062 (20150401); Y10T
137/87249 (20150401) |
Current International
Class: |
F16K
11/20 (20060101); F16K 31/145 (20060101) |
Field of
Search: |
;604/891.1 ;128/903
;137/597 ;251/61.1 |
References Cited
[Referenced By]
U.S. Patent Documents
Primary Examiner: Lucchesi; Nicholas D.
Assistant Examiner: Maiorino; Roz
Attorney, Agent or Firm: Townsend and Townsend and Crew
LLP
Parent Case Text
CROSS REFERENCE TO RELATED APPLICATION
This application is a nonprovisional of, and claims the benefit of
the filing date of U.S. Provisional Appl. No. 60/380,784, entitled
"DRUG DELIVERY SYSTEM," filed May 13, 2002 by Avtar S. Nat, the
entire disclosure of which is incorporated herein by reference for
all purposes.
Claims
The invention claimed is:
1. An implantable drug delivery system, comprising: a housing; a
collapsible reservoir disposed in the housing; a microfabricated
flow channel connected at one end to the collapsible reservoir, and
further opening at an external surface of the housing; at least one
magnet disposed within the housing adjacent a membrane defining the
flow channel, the magnet being movable in response to a magnetic
force to deflect the membrane into the flow channel for inhibiting
drug flow from the collapsible reservoir to the external surface of
the housing, and for pumping drug flow from the collapsible
reservoir to the external surface of the housing, wherein the at
least one magnetic comprises: three magnets disposed adjacent the
membrane, the three magnets being capable of sequential activation,
each collapsing the flow channel in a region adjacent thereto,
thereby peristaltically pumping the drug through the flow
channel.
2. The implantable drug delivery system recited in claim 1, further
comprising an electromagnet disposed within the housing to provide
the magnetic force.
3. The implantable drug delivery system recited in claim 2, further
comprising a power source disposed within the housing and coupled
with the electromagnet.
4. The implantable drug delivery system recited in claim 1, wherein
a wall of the collapsible reservoir is adapted to collapse in
response to vacuum that is created as drug is depleted from the
reservoir and to take up space formely occupied by an expelled
amount of drug.
5. The implantable drug delivery system recited in claim 1, further
comprising an electromagnet disposed within the housing to provide
the magnetic force.
6. The implantable drug delivery system recited in claim 5, further
comprising a power source disposed within the housing and coupled
with the electromagnet.
7. The implantable drug delivery system recited in claim 1, wherein
a wall of the collapsible reservoir is adapted to collapse in
response to vacuum that is created as drug is depleted from the
reservoir and to take up space formely occupied by an expelled
amount of drug.
Description
The various drug delivery systems disclosed herein are ideally
suited for use with, and preferably incorporates various
microfabricated pump and valve systems as disclosed in U.S. Patent
Applications Ser. Nos. 60/186,856, filed Mar. 3, 2000; 60/147,199,
filed Aug. 3, 1999; 60/141,503, filed Jun. 28, 1999 and Ser. No.
09/605,520, filed Jun. 27, 2000.
Part I--an Implantable Drug Delivery Device
An exemplary embodiment of an implantable drug delivery device is
shown in FIG. 1. It consists of a implant, (which may preferably be
cylindrical in shape) which preferably also comprises the following
features. 1. A protective outer housing that prevents any
deformation of the structure during implantation and in-use life.
2. A pre-filled drug reservoir that opens into one or more delivery
micro flow channels 3. A battery operated pump module with flow
control logic.
The protective housing can be made from any biologically inert
material that will prevent buckling of the drug reservoir during
implantation and while the delivery system is in use. The delivery
end of this housing has openings (which may in a exemplary aspect
be circular or rectangular) to allow the micro flow channels (which
are connected to the drug reservoir) to discharge the drug into the
patient's body. The circular area of the protective housing may be
solid. The drug-reservoir end of the housing preferably has one or
more circular openings or an optional mesh-like structure to both
protect the drug reservoir during handling, implantation, and use,
and to allow the reservoir wall to collapse when drug has been
depicted from it. An example of a biologically inert material is
titanium.
An advantage of having a collapsible drug reservoir is that, as the
drug is pumped out of the reservoir (by the present microfabricated
pump/vale system), a negative pressure is not created in the drug
reservoir.
The drug reservoir and micro flow channels are created as an
integrated, monolithic structure using soft lithography from any of
the elastomers that are compatible with a specific drug, and
according to any of the systems set forth in U.S. Patent
Applications Ser. Nos. 60/186,856, filed Mar. 3, 2000; 60/147,199,
filed Aug. 3, 1999; 60/141,503, filed Jun. 28, 1999 and Attorney
Docket No. 20174-00230, filed Jun. 27, 2000.
The delivery end of the micro channels (through which the drug is
pumped from the drug reservoir to the surface of the device) may be
terminated with any suitable valve structure, for example a duck
bill narrow diameter valve or a flap valve. These valves will
normally remain closed and will open under the fluid pressure of
the drug during expulsion from the micro flow channels. The present
integrated, monolithic structure also houses several micro magnets
that are located alongside of membranes that serve as shut off
valves for the micro flow channels.
The battery operated pump module with flow control logic consists
of a cylindrical structure that includes a battery, a programmable
IC chip, and several electromagnets. The pump module is
hermetically sealed and is assembled with the drug reservoir prior
to encapsulation within the protective housing. The pumping
dynamics will determine the flow rate within each micro flow
channel and the total delivery rate is determined by the number of
micro flow channels.
Depending on the program logic, the implantable drug delivery
system can provide controlled release, pulsatile delivery, or
programmable delivery (such as delivery only at certain times of
day, or only on certain days). The size of the drug reservoir will
determine the total amount of drug delivered and the duration of
such delivery. In a preferred aspect of the present invention, as
the drug is depleted from the reservoir, one wall of the reservoir
collapses due to the vacuum that is created and takes up the space
formerly occupied by the expelled amount of drug, in a manner
similar to a bag of IV solution.
In optional aspects of the invention, the exit of the micro
channels could also be terminated with a micro bore tubing which
extends from the device, acting as a catheter for delivery to a
site that may be hard or undesirable to access with the implantable
drug delivery system (ie: a site where it is difficult to position
the implantable drug delivery system).
The implantable drug delivery system described above could also
optionally be positioned external to the body and connected by way
of a micro bore catheter to deliver the drug to specific site
within the body.
FIGS. 3, 4 and 5 illustrate an exemplary system of operation of the
present device. As seen in FIG. 3, (and the breakaway close-up view
of FIG. 4) a plurality of electromagnets EL1, EL2 and EL3 are
provided. When electromagnets EL1, EL2 and EL3 are energized (under
control of the IC Circuit of FIG. 1 and with power from the battery
of FIG. 1) magnets M1, M2 and M3 move in radial directions D1, as
shown.
In a preferred aspect of the present invention, the electromagnets
EL1, EL2 and EL3 are activated in sequence (FIG. 5 shows only EL3
activated, pushing M3 in direction D1, thereby pinching off flow
through the flow channel passing from the drug reservoir into the
patient's body such that the drug is peristaltically pumped through
the flow channel into the patient's body.
It is to be understood that peristaltic pumping can be achieved by
magnetic actuation (as illustrated in FIGS. 1, 3, 4 and 5, and also
by pneumatic actuation, as described in U.S. Patent Applications
Ser. Nos. 60/186,856, filed Mar. 3, 2000, 60/147,199, filed Aug. 3,
1999; 60/141,503, filed Jun. 28, 1999 and filed Jun. 27, 2000. In
an example of pneumatic actuation, at least 3 control channels
(which arc disposed adjacent the flow channel, crossing over the
flow channel such that an elastomeric membrane disposed
therebetween is deflected into the flow channel when the control
channel(s) are pressurized) can also be used to peristaltically
pump fluid through the flow channel. In addition to pneumatic and
magnetic actuation, electrostatic actuation is also contemplated.
For example, as shown in FIG. 6 (and the break away close up of
FIG. 7), opposite electroded surfaces E1 and E2 may be energized
such that they repel one another, and thereby move apart from one
another, causing E1 to deflect into the flow channel.
In the various aspects of the invention in which magnets M or
electroded surfaces E are used for peristaltic pumping, the present
structure preferably comprises a multi-layer elastomeric block,
with a portion of the elastomeric block comprising a membrane which
either separates the control channel from the flow channel, or
separates a portion of the elastomeric block in which a magnet M or
an electroded surface E, thereby permitting movement of the portion
of the block comprising magnet M or an electroded surface E into
the flow channel.
Part II--Transdermal Delivery of Medicinal Agents
In another aspect of the invention, a monolithic microfabricated
pump/valve system can be used to deliver a medicinal agent through
the stratum corneum of the skin, akin to a transdermal patch. In
this aspect of the present invention, the present system is placed
at an external location on the patient's body and the system
delivers drugs directly to the surface of the patient. The drug(s)
then diffuse into the patient's body through the stratum corneum.
Various optional techniques are available to enhance the transport
rate through the skin barrier. These include, for example, the use
of permeation enhancers and/or the disruption of the stratum
corneum by mechanical or other means.
The present transdermal delivery system can also be used to meter
precise amounts of a drug for delivery at a predetermined rate
and/or delivery profile. This rate of delivery could be modified as
desired. An exemplary embodiment of such a device would he similar
to the implantable device shown in FIG. 1, however, the aspect
ratio could be such that the diameter of the cylinder is instead
much larger than the height of the device such that the system can
be easily worn like a transdermal patch on the skin.
Part III--Transdermal Body Fluid Sampling and Diagnosis
FIG. 2 illustrates a transdermal body fluid sampling device in
accordance with the present invention. One exemplary use of such a
device would be to measure glucose in interstitial body fluids to
determine when and if to deliver insulin in diabetes management. In
one embodiment of such a device, a thin gel layer is located
underneath an array of micro channels that lead to a single flow
channel (which is in turn connected to the drug reservoir). Within
this larger channel is a sensor that measures the amount of glucose
in interstitial body fluid.
Upon actuation, the larger flow channel will create a vacuum that
will assist the flow of IBF into the array of micro channels and
then allow it to flow past a sensor located inside the larger
channel. The sensor will measure the amount of glucose and display
the results.
The present invention also comprises systems which combine a
sampling system with a drug delivery system (and link them to
provide sensing-loop controlled drug delivery). In the case of
insulin delivery, for example, this would be a tremendous benefit
in diabetes management.
Part IV--Exemplary Drugs
In accordance with the present invention, any suitable drug may be
dispensed. This list of drugs includes, but is not limited to the
following:
Therapeutic Drugs:
Central Nervous System Cardiovascular Inner Ear Oncology Ocular
Tissue Engineering Neurological Inner Cranial Rheumatoid Arthritis
Parkinson's Diseases Contraception Anti-Epileptics Anemia Diabetes
Multiple Sclerosis Schizophrenia AIDS Infections Other: Chemical
Make-up Small Molecule Protein (large molecule)
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